Polyamines are intimately linked to the growth of mammalian cells. Many changes in cellular metabolism induced by hormones and other agents are accompanied by marked increases in the rate of synthesis of putrescine and spermidine brought about by increases in the activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase. The proposed experiments will extend knowledge of these enzymes (which have interesting regulatory properties and very rapid apparent rates of synthesis and degradation). These enzymes will be purified to homogeneity by affinity chromatography on pyridoxamine phosphate and methylglyoxal bis(guanylhydrazone) linked to Sepharose respectively. The purified enzymes will be used to raise specific antibodies to the enzymes. Specific irreversible inhibitors of both enzymes (namely alpha-difluoromethylornithine and 1,1'-((methylethanediylidene)-dinitrilo))-bis(e-amino-guanidine)) will be used to test the role of these enzymes in cell growth and differentiation. Labeled forms of these inhibitors will be used to measure specific binding to the enzyme and the number of enzyme molecules. Polyamines are known to be important in the growth of normal and malignant cells and knowledge of the regulation of polyamine synthesis and the effects of depleting cellular polyamines may enable the development of useful cancer chemotherapeutic agents either from existing inhibitors or by the synthesis of new polyamine antagonists.